Triple-negative breast cancer is a highly aggressive tumor subtype that lacks effective therapeutic targets. Here, we show that ELK3 is overexpressed in a subset of breast cancers, in particular basal-like and normal-like/claudin-low cell lines. Suppression of ELK3 in MDA-MB-231 cells led to transdifferentiation from an invasive mesenchymal phenotype to a non-invasive epithelial phenotype both in vitro and in vivo. Suppression of ELK3 resulted in extensive changes in genome expression profiles. Among these, GATA3, a master suppressor of metastasis, was epigenetically activated. Also, suppression of GATA3 led to the restoration of migration and invasion. These results suggest that the ELK3-GATA3 axis is a major pathway that promotes metastasis of MDA-MB-231 cells.

Tumor-associated lymphatic vessels (LV) serve as a route of cancer dissemination through the prometastatic crosstalk between lymphatic endothelial cells (LECs) lining the LVs and cancer cells. Compared to blood endothelial cell-derived angiocrine factors, however, LEC-secreted factors in the tumor microenvironment and their roles in tumor metastasis are poorly understood. Here, we report that ELK3 expressed in LECs contributes to the dissemination of cancer cells during tumor growth by providing oncogenic miRNAs to tumor cells through exosomes. We found that conditioned medium from ELK3-suppressed LECs (LCM) lost its ability to promote the migration and invasion of breast cancer cells such as MDA-MB-231, Hs578T and BT20 in vitro . Suppression of ELK3 in LECs diminished the ability of LECs to promote tumor growth and metastasis of MDA-MB-231 in vivo . Exosomes derived from LECs significantly increased the migration and invasion of MDA-MB-231 in vitro , but ELK3 suppression significantly diminished the pro-oncogenic activity of exosomes from LECs. Based on the miRNA expression profiles of LECs and functional analysis, we identified miR-503-3p, miR-4269 and miR-30e-3p as downstream targets of ELK3 in LECs, which cause the above phenotype of cancer cells. These findings strongly suggest that ELK3 expressed in LECs is a major regulator that controls the communication between the tumor microenvironment and tumors to support cancer metastasis.

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Pd takes various chemical forms according to the types of catalysts and even its pristine chemical state is often subject to change in operation. To understand the mechanism how Pd-based catalysts activate reactions, it is important to have a capability to identify the surface chemical state of Pd-based catalysts in contact with reactants. In this study, we conducted in situ near ambient pressure-x-ray photoelectron spectroscopy (NAP-XPS) in gas conditions with water and oxygen for hydrous Pd oxide, which is also known as palladium hydroxide (Pd(OH)2) and it is the key component of the Pearlman’s catalyst widely used for organic reactions. We found that hydrous Pd oxide showed different spectral features to that of anhydrous Pd oxide under gaseous water environments. We believe that this NAP-XPS study provides new information for a better identification of hydrous Pd oxide under reaction conditions, which is not available from conventional XPS in ultrahigh vacuum.

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